Catherine Kier

Barriers to adherence to cystic fibrosis infection control guidelines

In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence‐based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients.

Clinical Sensitivity of Cystic Fibrosis Mutation Panels in a Diverse Population

Infants are screened for cystic fibrosis (CF) in New York State (NYS) using an IRT‐DNA algorithm. The purpose of this study was to validate and assess clinical validity of the US FDA‐cleared Illumina MiSeqDx CF 139‐Variant Assay (139‐VA) in the diverse NYS CF population. The study included 439 infants with CF identified via newborn screening (NBS) from 2002 to 2012. All had been screened using the Abbott Molecular CF Genotyping Assay or the Hologic InPlex CF Molecular Test. All with CF and zero or one mutation were tested using the 139‐VA. DNA extracted from dried blood spots was reliably and accurately genotyped using the 139‐VA. Sixty‐three additional mutations were identified. Clinical sensitivity of three panels ranged from 76.2% (23 mutations recommended for screening by ACMG/ACOG) to 79.7% (current NYS 39‐mutation InPlex panel), up to 86.0% for the 139‐VA. For all, sensitivity was highest in Whites and lowest in the Black population. Although the sample size was small, there was a nearly 20% increase in sensitivity for the Black CF population using the 139‐VA (68.2%) over the ACMG/ACOG and InPlex panels (both 50.0%). Overall, the 139‐VA is more sensitive than other commercially available panels, and could be considered for NBS, clinical, or research laboratories conducting CF screening.

Utility of a very high IRT/No mutation referral category in cystic fibrosis newborn screening

Newborn screening for Cystic Fibrosis (CF) began in New York in October, 2002 using immunoreactive trypsinogen (IRT)/DNA methodology. Infants with at least one CFTR mutation or very high IRT and no mutations (VHIRT) are referred for sweat testing. In a preliminary analysis, we noted a very low positive predictive value (PPV) and preponderance of Hispanic infants in the group of infants with CF referred for VHIRT, which led to a decision to revise, but not eliminate, the VHIRT category. Automatic referral for specimens with VHIRT collected on the day of birth was eliminated, and the VHIRT threshold was raised from 0.2% to 0.1%. In this report, we describe outcomes from VHIRT referrals among 2.4 million infants screened between March 2003 and February 2013. Following the algorithm change, referrals decreased by 37.8% overall (annual mean 1,485 vs. 923), and the VHIRT PPV improved (0.6–1.0%). The number of infants diagnosed has remained consistent at 1 in 4,400 births. The proportion of Black/Hispanic/Asian/Other infants with confirmed CF, CFTR‐related metabolic syndrome (CRMS), or possible CF/CRMS was 21.3% in infants with 1–2 mutations, but 75.8% in the VHIRT group. In conclusion, although the PPV among VHIRT referrals remains low, had this category never been implemented, 24 infants with confirmed CF, and 9 infants with CRMS or possible CF/CRMS, most of whom were Hispanic, would have been missed over the 10 years. Information from this study may be helpful in assessing the need for the VHIRT category and algorithm changes in other screening programs. Pediatr Pulmonol. 2015; 50:771–780.

Childhood Overweight and Obesity and Their Association With Asthma

Poor diet, decreased physical activity, and obesity are emerging as determinants that may be critical in the cause of asthma. The obesity epidemic is a worldwide problem affecting both developed and developing countries. The prevalence of obesity among US children and adolescents has tripled over the past 4 decades, and there is an all-time low in the level of physical activity among children and adolescents. Recent data show that the incidence of asthma has been climbing rapidly as well over these past 4 decades. An increasing body of literature suggests that there is an association between this parallel rise of obesity and asthma incidences. Although the exact nature of this association remains unclear, many investigators have interpreted the data to suggest that obesity both increases the risk of incident asthma and alters prevalent asthma toward a phenotype that is more difficult to control.

Asthma and Sleep

Asthma significantly affects quality of sleep. Asthma physiology follows a diurnal pattern with peak flow at its lowest during early morning hours. The type and timing of release of inflammatory mediators also varies during the day and nighttime. Nocturnal symptoms are common in poorly controlled asthma. Hence, these nighttime symptoms play a significant role in the assessment of asthmatic patients as demonstrated in validated asthma control and quality of life questionnaires. Comorbid conditions may include allergic rhinitis, obesity, obstructive sleep apnea, and gastroesophageal reflux, all of which may worsen asthma symptoms, especially during sleep. In addition, exposure to greater loads of allergens in susceptible individuals during sleep is a significant problem and must be addressed to break the cycle of poor asthma control. Thus, asthma education for better symptom control should address these particular issues surrounding sleep.